Is SET p.Phe143= (c.429T>C) pathogenic?

SET p.Phe143= (c.429T>C) is classified Likely benign in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Rare (popmax 0.159%, sas).

How common is SET p.Phe143= (c.429T>C) in the general population?

SET p.Phe143= (c.429T>C) is rare (popmax 0.159%, sas) (gnomAD).

SET p.Phe143=

c.429T>C · VCV4084170

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.159%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1, phastCons 1
Overall
CADD	11.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.159% South Asian · 144/90,704 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.0193% 311/1,607,458 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.159%	630
Finnishnot grpmax-eligible	0.0797%	1,255
Middle Eastern	0.0496%	2,015
Remaining individualsnot grpmax-eligible	0.0112%	8,899
European (non-Finnish)	0.00894%	11,184
Admixed American	0.00167%	59,950

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SET
Protein: p.Phe143=
Coding: c.429T>C
MANE Select: NM_003011
Type: single nucleotide variant
Location: chr9:128692918 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 143: the 'earmuff domain' region

Full SET gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SET c.663+5G>C Pathogenic ★★ same type
SET p.His105Tyr Likely pathogenic ★★ same type
SET p.Asp224Asn Uncertain significance ★★ ⚠ same type
SET p.Asp260Glu Uncertain significance ★★ ⚠ same type
SET p.Glu261Asp Uncertain significance ★★ ⚠ same type
SET p.Phe189Cys Uncertain significance ★★ ⚠ same type
SET c.132-17C>T Benign ★★ same type
SET c.493-14C>T Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/set-p-phe143 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown